Document Detail


Simvastatin suppresses homocysteine-induced apoptosis in endothelial cells: roles of caspase-3, cIAP-1 and cIAP-2.
MedLine Citation:
PMID:  19343037     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study addresses how homocysteine (Hcy) induces endothelial apoptosis and how simvastatin antagonizes these pro-apoptotic effects of Hcy.Human umbilical vein endothelial cells (HUVECs) were treated with Hcy for 24 h, in the presence or absence of simvastatin. Cell apoptosis was evaluated by Annexin V staining and flow cytometry, as well as transferase-mediated dUTP-biotin nick end labeling (TUNEL). The mRNA and protein levels of caspase-3, cellular inhibitor of apoptosis (cIAP)-1 and -2 were analyzed by real-time polymerase chain reaction (RT-PCR) and western blotting, respectively.Treatment with both low (0.05 mmol l(-1)) and high (0.3 mmol l(-1)) concentrations of Hcy induced apoptosis in HUVECs which was accompanied by an increased level of caspase-3 expression and activation, together with decreased cIAP-1 and cIAP-2 levels. Conversely, simvastatin upregulated c-IAP1 and c-IAP2 expression, while attenuating Hcy-induced apoptosis and caspase-3 activation. Hcy may induce HUVEC apoptosis through a pathway involving caspase-3. This induction can be partially antagonized by simvastatin, possibly through upregulation of cIAP-1 and cIAP-2.
Authors:
Zhihong Xu; Guoping Lu; Fang Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-03
Journal Detail:
Title:  Hypertension research : official journal of the Japanese Society of Hypertension     Volume:  32     ISSN:  1348-4214     ISO Abbreviation:  Hypertens. Res.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-06     Completed Date:  2009-11-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  375-80     Citation Subset:  IM    
Affiliation:
Department of Geriatrics, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Caspase 3 / genetics,  metabolism
Cells, Cultured
Endothelium, Vascular / drug effects*,  metabolism
Homocysteine / antagonists & inhibitors*,  metabolism,  pharmacology
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Hyperhomocysteinemia / metabolism
Inhibitor of Apoptosis Proteins / genetics,  metabolism
Simvastatin / pharmacology*
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Inhibitor of Apoptosis Proteins; 454-28-4/Homocysteine; 79902-63-9/Simvastatin; EC 3.4.22.-/Caspase 3

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